The invention relates to a new class of compounds, a pharmaceutical composition thereof, a method of preparing a medicament for the treatment of a cancer, and a method of treating cancers. It finds particular application in conjunction with the treatment of breast cancer, colon cancer, CNS cancer, leukemia, melanoma, non-small cell lung cancer, ovarian cancer, renal cancer, and prostate cancer, and will be described with particular reference thereto. However, it is to be appreciated that the present exemplary embodiment is also amenable to other like applications.
Epidemiological and animal model studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may also act as chemopreventive agents. The premise that cyclooxygenase-2 (COX-2) inhibition is integral to this anticarcinogenic effect is based on the assumption that COX-2 generated prostaglandins (PGEs) promote tumor growth in an autocrine and/or paracrine manner. The inhibition of COX-2 activity by traditional NSAIDs blocks these activities and thus may account for the anticarcinogenic activity of these drugs. However, an expanding body of evidence suggests that COX-2-independent mechanism may also be involved in the antitumor effect of COX-2 inhibitors.
Nimesulide (4-nitro-2-phenoxymethane-sulfoanilide) is a nonsteroidal anti-inflammatory drug with a preferential COX-2 inhibitory activity and has been available in some Asian and European countries since 1985. Furthermore, some studies have also demonstrated the anti-cancer activity of nimesulide during the past decade. For example, U.S. Pat. No. 7,741,520 issued to Brueggemeier et al. has disclosed that some sulfonanilide analogs can be used as selective aromatase modulators (SAMs) to suppress aromatase activity expression in breast cancer cells. Nimesulide can induce apoptosis in liver and lung cancer cells, and it also suppresses the development of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP)-induced mammary gland carcinogenesis in rats. However, problems associated with nimesulide and its known derivatives include that, as general anti-cancer agents, they exhibit only low to moderate potency on a narrow range of cancers.
Advantageously, the present invention provides a new compound, a pharmaceutical composition containing the compound, a method of preparing a medicament for the treatment of a cancer using the compound, and a method of treating a cancer. The invention overcomes the aforementioned problems, and exhibits merits against cancers such as significantly higher potency, and effectiveness over a broader range of cancers, among others.